PDF - National Association of Orthopaedic Technologists

9/18/14
Low Intensity Pulsed
Ultrasound Bone
Stimulation
Application and Integration for Your
Practice
Michael C. McGlamry DPM, FACFAS
Forsyth Foot & Ankle
Cumming, GA
Agenda
•  Incidence of fractures in the US
- Risk factors that impact fracture healing
•  EXOGEN® Ultrasound Bone Healing
System
- Description
- Mechanism of action
- Clinical evidence
- Economic and other considerations
EXOGEN is a registered trademark of Bioventus LLC.
•  Incorporating EXOGEN into your clinical
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Incidence of fractures in the US
A common and continuing
healthcare concern
US fracture incidence
1
• 15.3 million fractures occur annually resulting in 14 million visits to emergency
2
rooms or other healthcare facilities
• Fractures account for more than half (53%) of all hospital discharges
3
• 2 million long-bone, 581,000 lower-leg, and 345,000 scaphoid fractures occur
4-6
annually
US delayed or non-union incidence
• 5% to 10% of all fractures are delayed or non-unions7
US expenditure for fracture treatment
• Treating fractures accounts for nearly half of the $56 billion annual expenditure for
8
trauma
1. AAOS Now. http://www.aaos.org/news/aaosnow/apr09/clinical9.asp. 2. Nolte PA, et al. J Trauma. 2001;51(4):693-703. 3. Bergen G, et al. Injury in the United States: 2007 Chartbook. 2008. http://www.cdc.gov/nchs/
data/misc/injury2007.pdf. 4. Cleveland KB. In: Campbell’s Operative Orthopaedics. 11th ed. 2007. 5. Wiss DA, et al. J Am Acad Orthop Surg. 1996;4(5):249-257. 6. Browner BD, et al. Skeletal Trauma: Fractures,
Dislocations, Ligamentous Injuries. 3rd ed. 2003. 7. Aaron RK, et al. Clin Orthop Relat Res. 2004;419:21-29. 8. National Trauma Data Bank Report (2002). The American College of Surgeons.
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Risk factors for impaired fracture
healing
Risk factor
(Approx. % of US
population)1-8
Fracture location
• Tibia
• Talus
• Clavicle
• Scaphoid
• Humerus
• Calcaneus
• Jones
• Pilon
• Advanced age
• Osteoporosis
• Obesity (33%)
• Smoking (22%)
• NSAID use (6%)
• Diabetes (8%)
• Steroid use, asthmatics
(3.7%)
Fracture personality
•  Fracture
displacement
•  Soft Tissue damage
•  Open/high energy
•  Comminuted
•  Segmented
•  Butterfly
1. US Census Bureau. http://www.census.gov. 2. Osteoporosis fast facts. http://www.nof.org/osteoporosis/diseasefacts.htm. 3. JAMA. 2005;294(2):172-173. 4. MMWR. 2005;52:509-513. 5. Fennerty MB. Postgrad Med.
2001;110:87-88, 91-94. 6. National Diabetes Information Clearinghouse. National diabetes statistics, 2007. http://diabetes.niddk.nih.gov/dm/pubs/statistics/index.htm#allages. 7. Agency for Healthcare Research and
Quality. MEPS statistical brief #13. http://www.meps.ahrq.gov/mepsweb/data_files/publications/st13/stat13.pdf. 8. American Lung Association. Trends in asthma morbidity and mortality. January 2009. http://
www.lungusa.org/atf/cf/%7B7a8d42c2-fcca-4604-8ade-7f5d5e762256%7D/ASTHMA%20JAN%202009.PDF.
Risk factor market research (n=99)
Soft tissue status
34%
Other
1%
Diabetes
16%
Obesity
1%
Age
6%
1
Smoking
25%
Fracture displacement
17%
DOF 12000.05
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EXOGEN Ultrasound Bone Healing
System
–  Indications*
•  Non-invasive treatment of established non-unions† excluding skull
and vertebrae
•  Accelerate time to healing for indicated fresh fractures in
skeletally mature individuals when managed by closed reduction
and cast immobilization
– Closed, posteriorly displaced distal radius
– Closed or Grade I open tibial diaphysis
  There are no known contraindications for the EXOGEN device. Safety and effectiveness has not been established
for individuals lacking skeletal maturity; pregnant or nursing women; patients with cardiac pacemakers; on fractures
due to bone cancer; or on patients with poor blood circulation or clotting problems. Some patients may be sensitive
to the ultrasound gel.
†A nonunion is considered to be established when the fracture site shows no visibly progressive signs of healing
EXOGEN description and mechanism of action
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What is Low-intensity pulsed
ultrasound?
•  A mechanical pressure
wave that produces a
biological response at the
cellular level
•  In a pre-clinical model
induces osteogenesis
through all stages of
fracture healing
•  Accelerates clinical and
radiographic healing1,2
1. Heckman JD, et al. J Bone Joint Surg Am. 1994;76(1):26-34.
2. Kristiansen TK, et al. J Bone Joint Surg Am. 1997;79(7):961-973.
1.
Intensity SATA (mW/cm2)
The EXOGEN Signal
EXOGEN Signal
1 msec (Pulsed Repetition Frequency = 1KHz)
200 µsec
(burst width)
Frequency 1.5MHz
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EXOGEN Ultrasound Depth and
Breadth of Penetration
Transducer
Soft
tissue
Depth of penetration (mm)
0
50
100
150
200
250
-60
-40
-20
0
20
40
60
Mathematical simulation of the ultrasound beam
penetrating soft tissue1.
1. Based on a mathematical simulation through soft tissue. DOF 12000.04
EXOGEN Ultrasound Depth and
Breadth of Penetration
Ultrasound
transducer
The EXOGEN signal travels through
bone
Bovine tibia
with sagittal cut
Bone marrow removed for
visualization purposes
Platform
The LIPUS beam goes through bone and into
marrow space
DOF 12000.04
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EXOGEN Ultrasound
The EXOGEN Ultrasound Bone Healing System is a noninvasive orthobiologic that works at the cellular level
1 Naruse K, et al. Prolonged endochondral bone healing in senescence is shortened by low-intensity pulsed ultrasound in a manner dependent on COX-2. Ultrasound Med Biol. 2010;36(7):1098–1108. 2 Leung KS, Cheung WH, Zhang C, Lee
KM, Lo HK. Low intensity pulsed ultrasound stimulates osteogenic activity of human periosteal cells. Clin Orthop Rel Res. 2004;418:253–259.3 Tang, CH, Yang, RS, Huang, TH, Lu, DY, Chuang, WJ, Huang, TF and Fu, WM (2006) Ultrasound
stimulates cyclooxy genase-2 expression and increases bone formation through integrin, focal adhesion kinase, phosphatidylinositol 3-kinase, and Akt pathway in osteoblasts, Molecular pharmacology 69(6):2047-57. 4 Sant’Anna EF, Leven
RM, Virdi AS, Sumner DR. Effect of low intensity pulsed ultrasound and BMP-2 on rat bone marrow stromal cell gene expression. J Orthop Res. 2005;23:646–652. 5 Schofer M, Block JE, Aigner J, Schmelz A. Improved healing response in
delayed unions of the tibia with low-intensity pulsed ultrasound: results of a randomized shamcontrolled trial. BMC Musculoskelet Disord. 2010;11:229. doi:10.1186/1471-2474-11-229.
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When is it appropriate to initiate
EXOGEN?
  In pre-clinical studies EXOGEN has been shown to accelerate healing
1
at each stage of the fracture healing process with maximum impact
achieved when applied throughout the entire healing process
*
*
*
187 days
Max Torque (N*mm)
*
(n=33)
(n=34)
*P<0.01 compared to contralateral control
Note: Clinical relevance has not been determined.
1. Azuma Y, et al. J Bone Miner Res. 2001;16(4):671-680.
EXOGEN and metal fixation
(Non-union)
•  No negative effects in the presence
of metal implants1
•  Non-cavitating, non-thermal 2
•  No metal degradation 1
•  No effect on screw stability 3
or screw torque removal
EXOGEN is FDA-approved for use with all
fixation methods in non-unions and has no
known contraindications.
1. Lehmann JF, et al. Arch Phys Med Rehabil 1979;40:483-488. 2. Lotsova E, Mechanics of Composite Materials 1979;15:330. 3. Gersten, JW. Am Phys Med
1988;37:75-82.
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EXOGEN indicated* fresh fracture
Clinical data analysis
Clinical evidence — fresh fractures
(Heckman JD, et al)
•  Prospective, randomized, placebo-controlled, double-blind, multicenter
1
study
•  Acute closed or Grade I open tibia fractures—short oblique
or transverse fractures with <50% displacement
•  Treatment 20 min/day until healed (3 cortices bridged)
n=33
38% faster
n=34
Time to heal (days)
1. Heckman JD, et al. J Bone Joint Surg Am. 1994;76(1):26-34.
P=0.0001
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Clinical evidence — fresh fractures
(Cook SD, et al)
Incidence of delayed union
•  Study also showed that EXOGEN treatment reduced the incidence of
delayed tibial unions by 83%, reducing the need for secondary
procedures
1. Cook SD, et al. Clin Orthop Relat Res. 1997;337:198-207.
Clinical evidence—fresh fractures
(Kristiansen TK, et al)
•  Prospective, randomized, placebo-controlled, double-blind,
1
multicenter study
•  Acute distal radius fractures treated conservatively
•  Treatment 20 min/day until healed (3 cortices bridged)
n=30
38% faster
n=31
Time to heal (days)
P=0.0001
1. Kristiansen TK, et al. J Bone Joint Surg Am. 1997;79(7):961-973.
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Clinical evidence—fresh fractures
(Kristiansen TK, et al)
Loss of reduction
•  Study also showed EXOGEN treatment reduced volar angulation
•  Loss of fracture alignment (%) measured by degree of volar angulation
P=0.01
1. Kristiansen TK, et al. J Bone Joint Surg Am. 1997;79(7):961-973.
Non-union case study
  64 yo Female
 Teacher
 Symptomatic TB and HT 5
22
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S.C.
1 mo
DC: Non-Union
 40 yo Female
 5th met base Fx
 LIPUS 2° (at 1st F/U increased gap)
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DOI
1 month
2 months
3 months
4 months
EXOGEN non-union* clinical data analysis
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Non-unions: No universal
definition
Source
FDA
Rockwood and
Green
Skeletal Trauma
CMS
Definition
When the fracture site shows no visibly progressive signs of healing.
1
Failure to heal in 6 to 8 months (and several others cited).2-7
A fracture that, in the opinion of the treating physician, has no
possibility of healing without further intervention.8
≥2 sets of radiographs, obtained prior to starting treatment with the
osteogenic stimulator, separated by a minimum of 90 days. Each
radiograph set must include multiple views of the fracture site
accompanied by a written interpretation from a physician stating that
there has been no clinically significant evidence of fracture healing
between the 2 sets of radiographs.9
What is your definition?
When do you consider next steps?
1. PMA FDA letter of approval. 2. Moholkar KD, Ziran BH. In: Bucholz RW, et al, eds. Rockwood and Green’s Fractures in Adults. 6th ed. 2006:563-612. 3. Buckwater J, Cruess RL. In: Rockwood CA, Green DP, eds.
Rockwood and Green’s Fractures in Adults. 3rd ed. 1991:81. 4. Heppenstall RB. Fracture Treatment and Healing. 1980. 5. Marsh D. Clin Orthop Relat Res. 1998;355(suppl):S22-S30. 6. Rodriguez-Merchan EC, et al. Clin
Orthop Relat Res. 2004;419:13-20. 7. Rosacker JA, et al. Orthopedics. 1981;4:1353. 8. Browner BD, et al, eds. Skeletal Trauma: Fractures, Dislocations, Ligamentous Injuries. 3rd ed. 2003. 9. The Centers for Medicare &
Medicaid Services. National Coverage Determinations Manual. Pub. 100-03.
Clinical evidence—non-unions
(Mayr E, et al)
1
•  Prospective case series of 100 non-unions
•  Inclusion criteria: stable, vital fragments, no infection, atrophic or hypertrophic
fracture, >90 days from last surgery or treatment change, >120 days since
fracture
•  EXOGEN 20 min/day was the only change in treatment
Fracture Age
EXOGEN Heal
Rate
Non-union
680+187
86%
(31/36)
Atrophy
306+81
83%
(70/84)
Hypertrophy
475+140
100%
(16/16)
Healing Disorder
86%
(n=33)
(n34)
1. Mayr E, et al. Unfallchirurg. 2002;105:108-115.
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Clinical evidence—non-unions
(Nolte PA, et al)
1
•  Prospective case series of 29 non-unions
•  5 Atrophic, 12 hypertrophic, 12 oligotrophic
•  Mean fracture age 1.2 years, mean time after last surgery 1 year
•  Average of 1.4 failed surgeries
Fracture Heal Rate
•  EXOGEN 20 min/day was the only change in treatment
n=29
1
n=9
n=13
. Nolte PA, et al. J Trauma. 2001;51(4):693-702.
Clinical evidence — non-unions
(Gebauer D, et al.)
1
•  Prospective case series of 67 non-unions
•  Inclusion criteria: stable, no infection, ≥8 months minimum fracture age, >4
months since last intervention, ≥3 months no radiographic healing
•  Mean fracture age 39 months; average of 2 failed surgeries
Fracture Heal Rate
•  EXOGEN 20 min/day was the only change in treatment
Completed Cases
ITT Analysis
1. Gebauer D, et al. Ultrasound Med Biol. 2005;31(10):1391-1402.
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Clinical evidence — non-unions
(Schofer et al.)
•  Level I - Randomize Controlled Trial
•  101 subjects with delayed union after tibia fracture >
4 months
•  Subjects randomized to either EXOGEN (n=51) or
sham (n=50)
•  EXOGEN arm increased bone mineral density (BMD)
by 34%
•  EXOGEN demonstrated significant reductions in
fracture gap
•  91% treatment compliance rate
31
Schofer M, Block JE, Aigner J, Schmelz A. Improved healing response in delayed unions of the tibia with low-intensity pulsed
ultrasound: results of a randomized shamcontrolled trial. BMC Musculoskelet Disord. 2010;11:229. doi:10.1186/1471-2474-11-229.
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EXOGEN effects on high-risk patients
EXOGEN and smoking
EXOGEN accelerates healing in
patients who smoke1
41% faster
n=34
n=30
0% of EXOGEN treated
smokers developed a delayed
union1
51% faster
n=31
Incidence of delayed union (percent)
n=33
158
132
33%
0%
0/14
Time to heal (days)
6/18
P<0.02
1. Cook SD, et al. Clin Orthop Relat Res. 1997;337:198-207.
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Effectiveness of EXOGEN in
younger and older patients
33% Faster
84 days
(n=13)
126 days
(n=15)
45% Faster
102 days
(n=13)
179 days
(n=15)
Heckman and Sarasohn-Kahn. 1997. Bulletin Hospital Joint Diseases 56(1):63–72
EXOGEN and large fracture
gaps
Time to heal (days)
197
144
Days
110
Days
n=8
98
Days
n=11
51% Days
Faster
100
Days
n=16
n=12
n=9
Fracture gap (millimeters)
Data on file: 12000.03
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Other EXOGEN non-union studies1
(Frankel & Mizuno)
•  EXOGEN Non-union registry of 1,546 patients
•  Demonstrated that for patients with risk factors that may impair
fracture healing, such as: substance abuse, diabetes, vascular
problems, or steroid use, there was no significant change in the
efficacy of EXOGEN Ultrasound
•  High success rates were achieved with EXOGEN for all bones,
regardless of fracture age
• 
A trend towards higher success rates and faster healing with earlier
intervention with EXOGEN
1.
EXOGEN Package Insert.
Frankel VH, Mizuno K. Management of nonunion with pulsed, low-intensity ultrasound therapy-international results. Surg Technol Int. 2001;
EXOGEN Ultrasound
 Economic and other considerations
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Economics of treating fresh tibia
fractures
Rate of delayed/non-union requiring surgery
(Heckman, Bull Hosp. Jt Dis,1997)
• 
Analysis of treatment costs
associated with tibial shaft fractures
• 
Evaluated surgery, emergency
room, workers compensation,
outpatient and device costs
• 
Savings with EXOGEN $15,219
• 
40% savings per case
With EXOGEN Without EXOGEN
Heckman and Sarasohn-Kahn. 1997. Bulletin Hospital Joint Diseases 56(1):63–72
Next Generation EXOGEN Treatment Calendar Screen
A 20-minute treatment was not completed
A 20-minute treatment was completed
Patient Treatment Compliance %
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Bone Healing Systems – Comparison Chart
Recommended
Daily treatment
times
Technology
EXOGEN
Bioventus
20 Minutes
Low-intensity
pulsed ultrasound
Biomet® Osteogen®
24 Hours
Direct electrical current
(implanted)
Orthopak® 2 Bone
Growth Stimulator
24 Hours
Capacitive coupling
EBI® Bone Healing
System®
10 Hours
Pulsed electromagnetic
field
Physio-Stim®
Orthofix
3 Hours
(minimum)
Pulsed electromagnetic
field
DonJoy®OL1000
30 Minutes
Combined magnetic
field
Product
manufacturer
Biomet
Indications
Fresh fracture
Non-union
Biomet
Biomet
dj Orthopedics
All trademarks referenced are the registered trademarks of their respective companies.
† EXOGEN PMA 900009: n=61, n=67 – 10/05/1994 †† EXOGEN PMA 900009: n=74, Supplement – 02/23/2000 ** EBI PMA P790005: Study 1: 66.7% healed, n=30; Study 2: 38.8% healed, n=58 – 01/25/1980
‡ Bioelectron PMA P850022: n=69 – 02/18/1986 ‡‡ EBI PMA P790002: Based on a four-year FDA follow-up, n=146 – 11/06/1979
µµ Orthofix/AME PMA P850007: 02/21/1986 27 Includes inconsistent users, defined as the cohort whose average usage (1.1 hours/day) was significantly below recommended protocol (8.0 hours/day) n=14.
28 Includes consistent users, defined as the cohort whose average usage (7.1 hours/day) was not significantly different from the recommended protocol (8.0 hours/day) n=135. § Orthologic PMA P910066: n=84 –
03/04/1994
Incorporating EXOGEN into
clinical practice
  Trust the science
  Extensive peer-reviewed research demonstrates the safety and
effectiveness of LIPUS for non-unions**and accelerated healing of
indicated* fresh fractures
  Select appropriate patients and fracture types
  Non-unions* (excluding skull and vertebrae), including:
–  Patients with certain risk factors or who want to return to normal activities faster
–  Patients who are unsuitable for surgery
  Indicated* fresh fractures
  Note the CPT code
  The billing code for treatment with EXOGEN is E0760
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G.L. 50 y.o. male
G.L.
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G.L. 3.5 mo Post EXOGEN
Locking Application
 S/P
– Chielectomy
– Implant arthroplasty
 Sub 2 pain
“My second toe is getting longer”
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4 Months Post Op
6 Months Post Op w/
EXOGEN
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56 Female Nonunion Akin Osteotomy
6 Months Post-op
102 Days EXOGEN
EXOGEN #1 in fracture
stimulation worldwide1
•  Accelerates healing of indicated* fresh
fractures-38%2,3
•  High heal rate for non-union* fractures 86%4
•  Unique Ultrasound technology
•  Effective in just 20 minutes a day
1. Based on company reports for global sales Jan –Dec 2012.
2. Heckman JD, Ryaby JP, McCabe J, Frey JJ, Kilcoyne RF. Acceleration of tibial fracture-healing by noninvasive, low-intensity pulsed ultrasound. J Bone Joint Surg. 1994;76-A(1):26–34.
3.. Kristiansen TK, Ryaby JP, McCabe J, Frey JJ, Roe LR. Accelerated healing of distal radial fractures with the
use of specific, low-intensity ultrasound. J Bone Joint Surg. 1997;79-A(7):961–973.
4. Premarket Approval P900009/Supplement 6, Summary of Safety and Effectiveness Data.
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Thank you!
28